Cellulitis

Jowhara Al-Qahtani, MD, Amer Homsi, MD and Bakr Nour, MD, PhD, FACS Reviewed 07/2016
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Subject: Cellulitis

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BASICS

DESCRIPTION

  • An acute bacterial infection of the dermis and subcutaneous tissue

  • Types and locations:

    • Periorbital cellulitis: bacterial infection of the eyelid and surrounding tissues (anterior compartment)

    • Orbital cellulitis: Infection of the eye posterior to the septum; sinusitis is the most common risk factor.

    • Facial cellulitis: preceded by upper respiratory infection or otitis media

    • Buccal cellulitis: infection of cheek in children associated with bacteremia (common before Haemophilus influenzae type B vaccine)

    • Peritonsillar cellulitis: common in children associated with fever, sore throat, and “hot potato” speech

    • Abdominal wall cellulitis: common in morbidly obese patients

    • Perianal cellulitis: sharply demarcated, bright, perianal erythema

    • Necrotizing cellulitis: gas-producing bacteria in the lower extremities; common in diabetics

  • System(s) affected: skin/exocrine

EPIDEMIOLOGY

  • Predominant sex: male = female (common in elderly and adults, except perianal cellulitis which is common in children)

  • All-cause mortality for patient admitted with cellulitis is 7%. Recurrence rate of cellulitis is 8–20% (1)[A].

Incidence

200/100,000 patient/years 

Prevalence

The exact prevalence is uncertain as cellulitis is common and not reportable. It affects all age groups and all races; however, certain types of cellulitis/microorganisms occur in certain populations. Community-acquired methicillin-resistant Staphylococcus aureus [CA-MRSA] has increased in athletes in contact sports (i.e., wrestling). 

ETIOLOGY AND PATHOPHYSIOLOGY

Cellulitis is caused by bacterial penetration through a break in the skin. Hyaluronidase mediates subcutaneous (SC) spread. 
  • Microbiology

    • β-Hemolytic streptococci (groups A, B, C, G, and F), S. aureus, including MRSA and gram-negative aerobic bacilli, are the most common.

    • S. aureus: periorbital and orbital cellulitis and IV drug users

    • Pseudomonas aeruginosa: diabetics and other immunocompromised patients

    • Aeromonas hydrophila and Vibrio vulnificus: cellulitis caused by waterborne pathogens

    • H. influenzae: buccal cellulitis

    • Clostridia and non–spore-forming anaerobes: necrotizing cellulitis (crepitant/gangrenous)

    • Streptococcus agalactiae: cellulitis following lymph node dissection

    • Pasteurella multocida and Capnocytophaga canimorsus: cellulitis preceded by bites

    • Streptococcus iniae: immunocompromised hosts

    • Rare causes: Mycobacterium, fungal (mucormycosis, aspergillosis, syphilis)

Genetics

No genetic pattern 

RISK FACTORS

  • Disruption of skin barrier: trauma, infection, insect bites, injection drug use, body piercing

  • Inflammation: eczema or radiation therapy

  • Edema due to venous insufficiency. Lymphatic obstruction due to surgical procedures or congestive heart failure

  • Elderly, diabetes, hypertension, obesity

  • Recurrent cellulitis:

    • Cellulitis recurrence score (2)[A]

    • Recurrent cellulitis is seen in immunocompromised patients (HIV/AIDS, steroids and TNF-α inhibitor therapy, diabetes, hypertension, cancer, peripheral arterial or venous diseases, chronic kidney disease, dialysis, IV or SC drug use (2)[A].

GENERAL PREVENTION

  • Good skin hygiene

  • Support stockings to decrease edema

  • Maintain tight glycemic control and proper foot care in diabetic patients.

DIAGNOSIS

Primarily a clinical diagnosis 

HISTORY

  • Previous trauma, surgery, animal/human bites, dermatitis, fungal infection; all serve as a portal of entry for bacterial pathogens.

  • Pain, itching, and/or burning

  • Fever, chills, and malaise

PHYSICAL EXAM

  • Localized pain and tenderness with erythema, induration, swelling, and warmth

  • Peau d’orange appearance

  • Regional lymphadenopathy

  • Purulent drainage (from abscesses)

  • Orbital cellulitis: proptosis, globe displacement, limitation of ocular movements, vision loss, diplopia

  • Facial cellulitis: malaise, anorexia, vomiting, pruritus, burning, anterior neck swelling

DIFFERENTIAL DIAGNOSIS

Toxic shock syndrome, venous stasis dermatitis (commonly mistaken as cellulitis), bursitis, acute dermatitis or intertrigo, herpes zoster or herpetic whitlow, deep vein thrombosis or thrombophlebitis, acute gout or pseudogout, necrotizing fasciitis or myositis, gas gangrene, osteomyelitis, erythema chronicum migrans or malignancy, drug reaction, sunburn, or insect stings. Spider bites and MRSA cellulitis can present similarly. 

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

  • If there are signs of systemic disease (fever, heart rate >100 bpm, or systolic blood pressure <90 mm Hg): blood cultures, CPK, CRP. Consider serum lactate levels.

  • WBC has 84% specificity and 43% sensitivity; whereas CRP had a sensitivity of 67% and specificity of 95% (PPV 95% and NPV 68%).

  • Aspirates from point of maximum inflammation yield 45% positive culture compared with 5% from leading edge

  • Blood cultures: Pathogens are isolated in <5% of patients. Blood cultures in children are more likely to show a contaminant than true positive.

  • Swab open cellulitis wounds for culture.

  • Plain radiographs, CT, or MRI are useful if osteomyelitis, fracture, necrotizing fasciitis, or retained foreign body is suspected or underlying abscess.

  • Gallium67 scintillography helps detect cellulitis superimposed on chronic limb lymphedema.

Diagnostic Procedures/Other

Consider lumbar puncture in children with H. influenzae type B or if meningeal signs and facial cellulitis. 

TREATMENT

GENERAL MEASURES

  • Immobilize and elevate the involved limb to reduce swelling.

  • Sterile saline dressings or cool aluminum acetate compresses for pain relief

  • Edema: compression stocking, pneumatic pumps. Diuretic therapy for CHF patients

  • Mark the area of cellulitis to monitor progression.

  • Tetanus immunization if needed, particularly if there is an open (traumatic) wound

MEDICATION

First Line

  • Target treatment in the setting of known pathogens or certain exposure (animal bites)

  • Antibiotic selection relies on clinical presentation:

    • Nonpurulent cellulitis

      • With nonpurulent drainage, target treatment toward β-hemolytic streptococci and MSSA.

      • Outpatient: treatment duration of 5 to 10 days

        • Oral: for mild cellulitis

          • Cephalexin 500 mg PO q6h; children: 25 to 50 mg/kg/day in 3 to 4 doses

          • Dicloxacillin 500 mg PO q6h; children: 25 to 50 mg/kg/day in 4 doses

          • Clindamycin 300 to 450 mg PO q6–8h; children: 20 to 30 mg/kg/day in 4 doses

        • IV: for rapidly progressing cellulitis

          • Cefazolin 1 to 2 g IV q8h; children: 100 mg/kg/day IV in 2 to 4 divided doses

          • Oxacillin 2 g IV q4h; children: 150 to 200 mg/kg/day IV in 4 to 6 doses

          • Nafcillin 2 g IV q4h; children: 150 to 200 mg/kg/day IV in 4 to 6 doses

          • Clindamycin 600 to 900 mg IV q8h; children: 25 to 40 mg/kg/day IV in 3 to 4 doses

  • Purulent cellulitis (probable CA-MRSA)

    • Culture all purulent wounds and follow up in 48 hours.

    • Incise and drain abscess and start empiric antibiotic therapy. Modify based on culture results; tailor duration based on clinical response (3)[B]:

      • Oral

        • Clindamycin 300 to 450 mg PO; children: 40 mg/kg/day in 3 to 4 doses

        • Trimethoprim-sulfamethoxazole (TMP-SMZ) 1 DS tab PO BID; children: dose based on TMP at 8 to 12 mg/kg/day divided in 2 doses

        • Doxycycline 100 mg PO BID; children >8 years of age: ≤45 kg: 4 mg/kg/day divided in 2 doses; >45 kg: 100 mg PO BID

        • Minocycline 200 mg PO once, then 100 mg PO BID; children >8 years old: 4 mg/kg PO once, then 4 mg/kg PO BID

        • Linezolid 600 mg PO BID; children <12 years: 10 mg/kg/dose (max 600 mg/dose) PO TID; ≥12 years: 600 mg PO BID

        • Tedizolid 200 mg PO once daily; children: Dosing is not established.

      • IV

        • Vancomycin 15 to 20 mg/kg/dose IV every 8 to 12 hours

        • Daptomycin 4 mg/kg/dose IV once daily; if bacteremia is present or suspected: 6 mg/kg IV once daily

        • Linezolid 600 mg IV BID

        • Tedizolid 200 mg IV once daily

        • Ceftaroline 600 mg IV q12h

        • Tigecycline 100 mg IV once, thereafter 50 mg IV q12h

  • Necrotizing cellulitis: requires broad-spectrum coverage to cover clostridial and anaerobic species: ampicillin-sulbactam 1.5 to 3.0 g q6–8h IV or piperacillin-tazobactam 3.37 g q6–8h IV plus ciprofloxacin 400 mg q12h IV plus clindamycin 600 to 900 mg q8h IV

  • Freshwater exposure: penicillinase-resistant: penicillin plus gentamicin or fluoroquinolone; in salt water exposure: doxycycline 200 mg IV in 2 divided doses

  • Bites: The combination of amoxicillin and clavulanic acid is recommended for human and dog bites. Ticarcillin and clavulanic acid or the combination of a 3rd-generation cephalosporin (i.e., ceftriaxone) plus metronidazole provides adequate parenteral therapy for animal or human bites. If allergic to penicillin, use fluoroquinolone plus metronidazole.

  • Facial cellulitis in adults: ceftriaxone IV

  • Diabetic foot infection: ampicillin/sulbactam or imipenem/cilastatin or meropenem; alternative: combinations of targeting anaerobes as well as gram-positive and gram-negative aerobes

  • If severe infection, toxicity, immunocompromised patients, or worsening infection despite empirical therapy, admit for empiric antibiotic therapy covering MRSA.

  • Recurrent streptococcal cellulitis: penicillin 250 mg BID, or if penicillin-allergic, use erythromycin 250 mg BID

Pediatric Considerations

  • Avoid doxycycline in children ≥8 years old and during pregnancy.

 

Second Line

Mild infection 
  • Penicillin allergy: erythromycin 500 mg PO q6h

  • Cephalexin remains a cost-effective therapy for outpatient management of cellulitis at current estimated MRSA levels.

SURGERY/OTHER PROCEDURES

  • Débridement for gas and purulent matter

  • Intubation or tracheotomy may be needed for cellulitis of the head or neck.

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

  • Severe infection, suspicion of deeper or rapidly spreading infection, tissue necrosis, or severe pain

  • Marked systemic toxicity or worsening symptoms that do not resolve after 24 to 48 hours of therapy

  • Patients with underlying risk factors or severe comorbidities

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

  • Repeat relevant labs (blood culture, CBC, potentially LP) if patient is toxic or not improving.

  • Consider deep vein thrombosis prophylaxis.

  • Cutaneous inflammation may worsen in the first 24 hours due to release of bacterial antigens. Symptomatic improvement usually occurs in 24 to 48 hours, but visible improvement may take 72 hours.

DIET

Glucose control in diabetics 

PATIENT EDUCATION

Good skin hygiene. 

PROGNOSIS

With adequate antibiotic treatment, prognosis is good. 
  • Low-dose penicillin prophylaxis in patients with recurrent cellulitis decreases recurrence (4)[A].

COMPLICATIONS

  • Local abscess or bacteremia, sepsis

  • Superinfection with gram-negative organisms

  • Lymphangitis, especially if recurrent

  • Thrombophlebitis or venous thrombosis

  • Bacterial meningitis

  • Gangrene

REFERENCES

Figtree M, Konecny P, Jennings Z, et al. Risk stratification and outcome of cellulitis admitted to hospital. J Infect.  2010;60(6):431–439.
Tay EY, Fook-Chong S, Oh CC, et al. Cellulitis recurrence score: a tool for predicting recurrence of lower limb cellulitis. J Am Acad Dermatol.  2015;72(1):140–145.
Champion AE, Goodwin TA, Brolinson PG, et al. Prevalence and characterization of methicillin-resistant Staphylococcus aureus isolates from healthy university student athletes. Ann Clin Microbiol Antimicrob.  2014;13(1):33.
Thomas KS, Crook AM, Nunn AJ, et al. Penicillin to prevent recurrent leg cellulitis. N Engl J Med.  2013;368(18):1695–1703.

ADDITIONAL READING

  • Brook I. Management of human and animal bite wounds: an overview. Adv Skin Wound Care.  2005;18(4):197–203.

  • Gunderson CG. Cellulitis: definition, etiology, and clinical features. Am J Med.  2011;124(12):1113–1122.

  • Kilburn SA, Featherstone P, Higgins B, et al. Interventions for cellulitis and erysipelas. Cochrane Database Syst Rev.  2010;(6):CD004299.

  • Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis.  2011;52(3):285–292.

  • Oh CC, Ko HC, Lee HY, et al. Antibiotic prophylaxis for preventing recurrent cellulitis: a systematic review and meta-analysis. J Infect.  2014;69(1):26–34.

  • Phoenix G, Das S, Joshi M. Diagnosis and management of cellulitis. BMJ.  2012;345:e4955.

  • Quirke M, O’Sullivan R, McCabe A, et al. Are two penicillins better than one? A systematic review of oral flucloxacillin and penicillin V versus oral flucloxacillin alone for the emergency department treatment of cellulitis. Eur J Emerg Med.  2013;21(3):170–174.

CODES

ICD10

  • L03.90 Cellulitis, unspecified

  • H05.019 Cellulitis of unspecified orbit

  • L03.211 Cellulitis of face

  • J36 Peritonsillar abscess

  • H05.012 Cellulitis of left orbit

  • H05.013 Cellulitis of bilateral orbits

  • L03.119 Cellulitis of unspecified part of limb

  • L03.221 Cellulitis of neck

  • L03.317 Cellulitis of buttock

  • L03.319 Cellulitis of trunk, unspecified

  • L03.818 Cellulitis of other sites

  • H05.011 Cellulitis of right orbit

ICD9

  • 682.9 Cellulitis and abscess of unspecified sites

  • 376.01 Orbital cellulitis

  • 682.0 Cellulitis and abscess of face

  • 475 Peritonsillar abscess

  • 682.1 Cellulitis and abscess of neck

  • 682.2 Cellulitis and abscess of trunk

  • 682.3 Cellulitis and abscess of upper arm and forearm

  • 682.4 Cellulitis and abscess of hand, except fingers and thumb

  • 682.5 Cellulitis and abscess of buttock

  • 682.6 Cellulitis and abscess of leg, except foot

  • 682.7 Cellulitis and abscess of foot, except toes

  • 682.8 Cellulitis and abscess of other specified sites

SNOMED

  • 128045006 cellulitis (disorder)

  • 109245003 Cellulitis of periorbital region

  • 200652002 cellulitis of face (disorder)

  • 102453009 Peritonsillar cellulitis (disorder)

  • 62837005 Cellulitis of hand

  • 128276007 Cellulitis of foot

  • 13680009 Cellulitis of forearm (disorder)

  • 287001000 Cellulitis of leg, excluding foot (disorder)

  • 37223007 Cellulitis of neck

  • 38217004 Cellulitis of upper arm (disorder)

  • 44428005 Cellulitis of buttock

  • 46876003 Cellulitis of trunk (disorder)

CLINICAL PEARLS

  • S. aureus and group A Streptococcus are the most common organisms that cause cellulitis.

  • Consider MRSA if cellulitis is not responding to antibiotics in the first 48 hours.

  • Rapid expansion of infected area with red/purple discoloration and severe pain may suggest necrotizing fasciitis, requiring urgent surgical evaluation.

 
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